Human natural killer (NK) cells and K cells mediating antibody-dependent cellular cytotoxicity have been shown to be large granular lymphocytess (LGL). The majority of LGL form lytic conjugates with a wide variety of NK-susceptible target cells. NK cytotoxic factors (NKCFs) are being examined for their specificity and mechanism of action. Three distinct steps have been defined for NKCF; a) production, b) binding to targets, and c) subsequent target lysis. With procedures able to independently measure these events, a variety of agents which have been reported to inhibit NK cell-mediated killing are being tested to determine their site of action. These NKCFs are produced by LGL and have a general specificity pattern similar to intact killer cells. Comparisons were made between NKCF and recombinant lymphotoxin (LT) and tumor necrosis factor (TNF). The results demonstrated that NKCF is distinct from both these cloned factors. In addition, LGL have been shown to produce a variety of cytokines including IFN-Alpha and Beta, interluekin 1 and 2, and B-cell growth factor in response to target cells or lectin. The effector cells for mediating antibody-dependent cellular cytotoxicity (ADCC) with various mouse monoclonal antibodies was shown to be associated with LGL. In addition, this ADCC effector cell was regulated in vitro by IFNs and IL-2 in a manner similar to the augmentation of NK activity.